The Makorin lep-2 and the lncRNA lep-5 regulate lin-28 to schedule sexual maturation of the C. elegans nervous system

Hannah Lawson, Edward Vuong, Renee M. Miller, Karin Kiontke, David Fitch, Douglas S. Portman

Research output: Contribution to journalArticle

Abstract

Sexual maturation must occur on a controlled developmental schedule. In mammals, Makorin3 (MKRN3) and the miRNA regulators LIN28A/B are key regulators of this process, but how they act is unclear. In C. elegans, sexual maturation of the nervous system includes the functional remodeling of postmitotic neurons and the onset of adult-specific behaviors. Here, we find that the lin-28-let-7 axis (the 'heterochronic pathway') determines the timing of these events. Upstream of lin-28, the Makorin lep-2 and the lncRNA lep-5 regulate maturation cell-autonomously, indicating that distributed clocks, not a central timer, coordinate sexual differentiation of the C. elegans nervous system. Overexpression of human MKRN3 delays aspects of C. elegans sexual maturation, suggesting the conservation of Makorin function. These studies reveal roles for a Makorin and a lncRNA in timing of sexual differentiation; moreover, they demonstrate deep conservation of the lin-28-let-7 system in controlling the functional maturation of the nervous system.

Original languageEnglish (US)
JournaleLife
Volume8
DOIs
StatePublished - Jul 2 2019

Fingerprint

Long Noncoding RNA
Sexual Maturation
Neurology
Nervous System
Sex Differentiation
Appointments and Schedules
Conservation
Mammals
MicroRNAs
Neurons
Clocks

Keywords

  • behavior
  • C. elegans
  • developmental biology
  • developmental timing
  • LIN28
  • lncRNA
  • neuroscience
  • reproductive maturation
  • sexual differentiation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

The Makorin lep-2 and the lncRNA lep-5 regulate lin-28 to schedule sexual maturation of the C. elegans nervous system. / Lawson, Hannah; Vuong, Edward; Miller, Renee M.; Kiontke, Karin; Fitch, David; Portman, Douglas S.

In: eLife, Vol. 8, 02.07.2019.

Research output: Contribution to journalArticle

Lawson, Hannah ; Vuong, Edward ; Miller, Renee M. ; Kiontke, Karin ; Fitch, David ; Portman, Douglas S. / The Makorin lep-2 and the lncRNA lep-5 regulate lin-28 to schedule sexual maturation of the C. elegans nervous system. In: eLife. 2019 ; Vol. 8.
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AU - Fitch, David

AU - Portman, Douglas S.

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